The present invention is related generally to medical devices. More specifically, the present invention is related to devices associated with delivery of genes or therapeutic substances.
A number of techniques are available for treating heart disease and diseases of other organs percutaneously. Examples of such techniques include delivery of genes and therapeutic substances, including the delivery of genes and therapeutic substances for percutaneous myocardial revascularization (PMR). This procedure is performed to increase blood perfusion through the myocardium of a patient. For example, in some patients, the number of lesions in coronary vessels is so great or the location so remote in the patient vasculature that restoring blood flow to the heart muscle is difficult. Percutaneous myocardial revascularization (PMR) has been developed as an alternative to techniques which are directed at bypassing or removing lesions. PMR is performed by boring holes directly into the myocardium of the heart. Positive results have been demonstrated in some human patients receiving PMR treatments. These results are believed to be caused in part by blood flowing from within a heart chamber through patent holes formed by PMR to the myocardial tissue. Suitable PMR holes have been proposed to be burned by laser, cut by mechanical means, and burned by radio frequency devices. Increased blood flow to the myocardium is also believed to be caused in part by the healing response to wound formation, specifically, the formation of new blood vessels in response to the newly created wound.
Several aspects of PMR procedures could be improved upon. One area for improvement is in the preparation of PMR injection catheters for use by the treating physician. In particular, at present, the PMR device maybe flushed with a drug to prime the distal needle by flushing the drug through the needle and into a container. This preparation can be awkward and may leave a container of biologically active material which may require further processing. Another aspect which may be further optimized lies in the attachment of the needle to the distal region of the PMR catheter tube. In particular, forces may act upon the needle during both the advancement and retraction of the needle within the heart wall, urging the needle undesirably both into and out of the tube. Improved methods of securing the needle to the tube would be desirable.
During a PMR treatment, a physician may be attempting to treat a three-dimensional space using a catheter having a distal bend. In particular, the physician may be attempting to treat the heart chamber side, anterior, and posterior wall regions. This may presently be difficult to visualize under fluoroscopy as current marking systems for shafts may make interpretation of the catheter distal region orientation somewhat ambiguous. The heart chamber wall thickness can vary depending on the chamber and wall region being treated. In particular, the left ventricle wall is thinner in the posterior region relative to the anterior region. Improved devices for variable depth, yet controlled penetration of the heart walls, would be advantageous. As multiple sites of the heart chamber wall are penetrated, a system for tracking the treated versus untreated regions would also be desirable.
The present invention includes improved devices and methods for performing PMR procedures. One device allows for improved preparation of PMR catheters used to inject a drug or therapeutic substance into the heart wall. One such device includes a PMR device distal region or hood disposed within the neck of a vial for receiving the drug. The vial can be used to receive the drug while the drug is being flushed through the PMR device and needle to prepare the PMR device for use. One vial has a neck and shoulder region for receiving and retaining the distal region of a PMR injection device. A no-leak gasket defines one wall of an inner cavity within one such vial.
The vial is preferably formed of a transparent or translucent material for observing the injection of the drug into the vial. In one embodiment, the vial cavity includes a drug-neutralizing agent. The agent allows the drug to be neutralized after receiving the drug. A neutralizing agent can provide improved safety, should the integrity of the vial be breached. The drug-neutralizing vial allows a biologically active drug to be flushed through the catheter with the vial being disposed of in a normal waste stream such as a wastebasket, rather than requiring special handling.
One set of devices provides improved needle attachment to drug delivery tubes. One improved drug delivery tube has an outer tube defining a lumen therein. A needle may be disposed within the distal end of the tube. The needle can have a distal, sharp tube region for insertion into the heart wall, as a well as a wider, more proximal region having outward protrusions for engaging or biting into the drug delivery tube inner wall. One device has a wide flange for abutting the drug delivery tube distal end, thereby limiting the proximal travel of the needle into the drug delivery tube lumen. One drug delivery tube also has a bonding hole which can be used to inject an adhesive to further secure the needle within the drug delivery tube distal region. The improved securing of the needle to the drug delivery tube can act to prevent the needle from being distally pulled from the tube.
During insertion of the needle into the heart wall, forces can act to urge the needle into the tube. Upon retraction of the needle from the heart wall, forces may act to pull the needle distally from the tube. Both the outward protrusions, the flange, and the added adhesive can act to better secure the needle to the drug delivery tube. One embodiment includes outward barbs biting into the drug delivery tube, while another embodiment uses a series of helically disposed screw threads to engage the tube wall. A preferred embodiment uses outward protruding elements which engage the inner wall, while another embodiment uses inwardly protruding elements engaging the outer wall of the tube distal region.
Another aspect of the invention provides improved visualization of the catheter shaft orientation under fluoroscopy. One embodiment utilizes asymmetrically disposed radiopaque markers on the shaft distal region to enable the treating physician to determine whether the catheter distal region is pointed at right angles to the treating physician or is pointed toward or away from the treating physician. One embodiment has the radiopaque marker being asymmetrically distributed with respect to a plane bisecting a longitudinal axis of the catheter tube distal region. Another embodiment further includes the radiopaque marker being asymmetrically distributed with respect to length over the catheter distal region. One marker includes an annular ring portion and a straight leg portion lying along the length of one side of the tube. Yet another embodiment includes an annular shell or ring portion and an annular arc leg portion extending along a length from the annular shell or ring portion. The radiopaque markers may be disposed on either the proximal or the distal side of any bend in the catheter shaft. A preferred use of the radiopaque marker band is on a guide catheter used to guide a PMR therapeutic tip to the heart wall.
In yet another aspect of the invention, radiopaque marker segments are asymmetrically distributed such that the rotation of the tube relative to the treating physician may be determined under fluoroscopy. One embodiment uses opposing annular shells on opposing sides of a tube where the annular shells are shifted longitudinally relative to each other. The asymmetrically disposed shells are thus asymmetric both with respect to a plane bisecting a longitudinal central access and with respect to a plane transversely bisecting a catheter shaft.
In still another aspect of the invention, marker bands are provided a distance apart which approximates the desired inter-treatment site spacing along the heart wall. A method can be performed using this aspect of the invention, whereby a therapeutic substance is delivered at treatment sites which are observed under fluoroscopy to be spaced apart approximately the distance between marker bands. Any distortion or magnification of the distances between marker bands will approximately be matched by distortions between treatment sites.
The present invention also includes a PMR device for allowing precise, variable depth needle penetration of the heart wall. One device includes at least one inner stop affixed to a rotatable inner needle. The device also can have one or more stops disposed inwardly from an outer tube, the outer tube having the inner needle rotatably disposed within. The inner needle can be longitudinally advanced until the inner stop abuts an outer stop, thereby inhibiting further distal movement of the inner needle. If greater penetration is desired, the inner shaft can be rotated, thereby swinging the inner stop clear of the first encountered outer stop, allowing the inner stop to proceed further distally until a subsequent outer stop is encountered. This aspect of the invention allows a single device to be used, yet provides multiple, preset, precise penetration depths. This may be of particular use where the thickness of the heart wall varies over different regions of the heart chamber wall.
Yet another aspect of the invention provides for injection of drug and contrast media into the heart wall. Injection of contrast media near the injection site of a drug allows the treating physician to visualize under fluoroscopy which areas of the heart wall have been treated and which have not yet been treated. One device provides a contrast media injection needle disposed side-by-side with a drug delivery needle. One embodiment allows the two side-by-side needles to be retracted and advanced together. The needles can be distally straight, arcuate, or one arcuate and one straight. Another embodiment provides a drug and contrast media injection device having a pair of needles, one being coaxially disposed within the other. The innermost needle can be used to inject drug deep into the heart tissue, while the more outer, coaxially disposed needle may be used to inject contrast media to the heart wall, thereby marking the site of treatment. One embodiment utilizes a sharp, cutting end to inject contrast media. Another embodiment uses a less sharp, less cutting end, for injecting a contrast media into the heart wall tissue using pressure, rather than cutting.